Magnetic resonance imaging (MRI) has long been used to create detailed internal images for use in medical diagnostics and treatment as well as studies of the brain and body. In MRI, a powerful magnetic field is used to align the magnetization of atomic nuclei in the body, and radio frequency is used to alter the alignment of the magnetization. The nuclei then produce a rotating magnetic field that is detectable by an MRI scanner and recordable to create images of the scanned area of the body. Over the years, various techniques have been developed to perform MRI scans that produce images for specialized diagnostics.
It is of great clinical interest to measure the temperature changes of deep-seated tissues non-invasively during the course of cancer thermotherapy (hyperthermia or high temperature thermal ablation), hypothermia treatment of acute ischemic stroke, and during triggered drug release from temperature-sensitive drug delivery systems. To date, a number of MRI techniques have been suggested for assessing temperature through, in addition to using temperature-sensitive MRI contrast agents, monitoring a particular MRI property that is responsive to temperature changes, including proton density, diffusion constants, T1 and T2 relaxation times, magnetization transfer ratio, and, the most widely used, water proton resonance frequency (PRF). Water PRF shifts are sensitive to temperature because it strongly affects the chemical shift of water protons by altering their hydrogen bonding state. Water PRF-based temperature measurement is plausible because of its relatively high sensitivity (−0.01 ppm/° C.) over a wide range of temperatures (−15 to 100° C.), which is tissue-type-independent except for adipose tissue. Water PRF methods using MRI have been implemented with two techniques, MR spectroscopic (MRS) imaging, and gradient-echo based phase mapping. Proton MRS directly determines the chemical shift of water protons by assessing the 1H NMR spectrum of the region of interest. Using non-temperature-responsive methyl and methylene protons (e.g. from N acetyl aspartate (NAA) or lipid) as reference, the absolute temperature can be determined after calibration. However, this technique is often limited by a low spatial or temporal resolution, and as such, not suitable for real-time monitoring. Alternatively, a high-resolution temperature change map can be obtained by assessing the difference in phase maps between two temperatures. To date, it is the most widely used non-invasive MRI method for temperature mapping in clinical and preclinical studies, with a capability of monitoring temperature change in real-time. However, the accuracy of measurement may be complicated when magnetic background gradient effects (e.g. due to changing shims) cannot be neglected or a significant portion of fat is present.
Recently, a so-called Water Saturation Shift Referencing (WASSR) method (30) was proposed to determine B0 shifts by assessing the minimum of the water direct saturation (DS) spectrum using a weak radiofrequency saturation. In such an approach, the B0 shift of each voxel is simply determined from a DS spectrum by finding the frequency that corresponds to the maximum saturation (or the weakest water signal intensity), using either a non-model-based maximal symmetry algorithm or a model-based Lorentzian line shape algorithm. The latter is possible because the steady-state direct saturation spectrum can be described exactly by a Lorentzian line shape.
It would therefore be advantageous to provide a method of MRI to map temperature changes if the temperature is the dominating factor causing the shift in B0. It would also be advantageous to provide a WASSR based temperature mapping MRI method, that can directly determine the chemical shift of water protons, similar to an MRS method, but with a higher temporal and spatial resolution and allow an unbiased assessment of water PRF in the presence of lipid protons without the need of a priori knowledge of fat composition and additional data processing steps.